Cardiovascular Autonomic Regulation,ETCO2 and the Heart Rate Response to the Tilt Table Test in Patients with Orthostatic Intolerance

Chronic orthostatic intolerance (COI) is defined by changes in heart rate (HR), blood pressure (BP), respiration, symptoms of cerebral hypoperfusion and sympathetic overactivation. Postural tachycardia syndrome (POTS) is the most common form of COI in young adults and is defined by an orthostatic increase in heart rate (HR) of?≥?30 bpm in the absence of orthostatic hypotension. However, some patients referred for evaluation of COI symptoms do not meet the orthostatic HR response criterion of POTS despite debilitating symptoms. Such patients are ill defined, posing diagnostic and therapeutic challenges. This study explored the relationship among cardiovascular autonomic control, the orthostatic HR response, EtCO₂ and the severity of orthostatic symptoms and fatigue in patients referred for evaluation of COI. Patients (N?=?108) performed standardized testing protocol of the Autonomic Reflex Screen and completed the Composite Autonomic Symptom Score (COMPASS-31) and the Fatigue Severity Scale (FSS). Greater severity of COI was associated with younger age, larger phase IV amplitude in the Valsalva maneuver and lower adrenal baroreflex sensitivity. Greater fatigue severity was associated with a larger reduction in ETCO₂ during 10 min of head-up tilt (HUT) and reduced low-frequency (LF) power of heart rate variability. This study suggests that hemodynamic changes associated with the baroreflex response and changes in EtCO₂ show a stronger association with the severity of orthostatic symptoms and fatigue than the overall orthostatic HR response in patients with COI.

     

真核基因转录与转录调节相关复合物

真核细胞核中转录因子与染色质模板如何相互作用调节基因转录是基因表达调控研究的一个中心问题.近来的研究表明,参与基因转录的各种调节因子在核内形成多种复合物,如RNA聚合酶Ⅱ全酶、染色质重塑复合物、核小体以及增强小体等.这些复合物之间相互作用,调节染色质结构,在染色质模板上进一步组装成转录复合物,参与转录调节的各个环节,调节转录复合物活性.这些复合物的形成,整合了转录调节的各种信息,提高了转录调节效率,是真核基因有效、严格、有序表达的基础.另一方面,这些复合物的存在给基因表达调控的研究提出了新问题,发展新的研究思路和新的研究技术具有重要意义.     

生境因子及理化因素对外源基因在植物体内表达的调节

外源基因在植物体内的表达除受植物体本身代谢及分子调节外,还受生境因子及理化因素等外界环境因子的调节.生境因子及理化因素可诱导植物某些基因的表达,同时调控这些基因的启动元件;利用营养及逆境胁迫条件改变植物的生长代谢也可实现对外源基因表达的调节.本综述了生境因子及理化因素对外源基因在转基因植物体内表达的调控机制.     

口服葡萄糖耐量试验负荷后1小时血糖筛查糖调节受损和糖尿病的最佳切点值及糖调节受损患者转归的随访研究

摘要 目的：研究分析口服葡萄糖耐量试验（OGTT）负荷后1 h血糖筛查糖调节受损（IGR）和糖尿病（DM）的最佳切点值及糖调节受损患者转归的随访结果。方法：选择2018年6月-2019年6月于西安交通大学第二附属医院行OGTT试验的340例受试者。采用受试者工作特征（ROC）曲线分析OGTT负荷后餐后1h血糖（1hPG）筛查DM及IGR的切点值。按照上述切点值将受试者分为正常组81例,IGR组106例,DM组153例。对比三组人员胰岛功能及血脂指标水平。对IGR组患者进行为期3年的随访观察,将其按照随访结果的差异分为进展组35例与无进展组71例。以单因素及多因素Logistic回归分析进展成DM的危险因素。结果：经ROC曲线分析,OGTT负荷后1hPG筛查IGR的最佳切点值为10.0 mmol/L,筛查DM的最佳切点值为13.0 mmol/L。正常组、IGR组及DM组胰岛素抵抗指数（HOMA-IR）、总胆固醇（TG）水平均呈逐渐升高趋势,β细胞功能指数（HOMA-β）呈逐渐降低趋势,且经单因素方差分析发现：各组间对比差异均有统计学意义（均P＜0.05）。进展组年龄、体质量指数（BMI）及TG水平均高于无进展组（均P＜0.05）。经多因素Logistic回归分析发现：年龄高、高BMI及高TG水平均是IGR患者进展成DM的独立危险因素（均P＜0.05）。结论：OGTT负荷后1 h血糖筛查IGR的切点值为10.0 mmol/L,筛查DM的切点值为13.0 mmol/L,且1hPG可有效反映胰岛功能及血脂水平。此外,IGR患者转归的影响因素与年龄、BMI及TG有关。     

The effect of acute warming and thermal acclimation on maximum heart rate of the common killifish Fundulus heteroclitus

Common killifish Fundulus heteroclitus were acclimated to ecologically relevant temperatures (5, 15 and 33°C) and their maximum heart rate (f_Hmax) was measured at each acclimation temperature during an acute warming protocol. Acclimation to 33°C increased peak f_Hmax by up to 32% and allowed the heart to beat rhythmically at a temperature 10°C higher when compared with acclimation to 5°C. Independent of acclimation temperature, peak f_Hmax occurred about 3°C cooler than the temperature that first produced cardiac arrhythmias. Thus, when compared with previously published values for the critical thermal maximum of F. heteroclitus, the temperature for peak f_Hmax was cooler and the temperature that first produced cardiac arrhythmias was similar to these critical thermal maxima. The considerable thermal plasticity of f_Hmax demonstrated in the present study is entirely consistent with eurythermal ecology of killifish, as shown previously for another eurythermal fish Gillichthys mirabilis.     

EDAG—1，一种与造血调控密切相关新基因的分离和确认

以代表性差异显示分析技术（RDA）获得一种在人胎肝组织中高丰度表达的胚胎发育相关基因1（embry-onic develop associated gene1,EDAG-1）,经筛选cDNA文库及5′末端cDNA快速扩增技术（rapid amplification of cDNA 5′end,5′RACE）获得其全长为2166bp的cDNA。该基因含编码484个氨基酸组成蛋白质的ORF,Blast检索表明编码蛋白质不含任何已知蛋白质功能结构域,与小鼠Hemogen及大鼠RP59基因同源。其mRNA3′端非释译区序列含2拷贝AUUUA结构,表明该基因mRNA稳定性差。体外翻译证明该基因编码蛋白质分子量为55.3kD,与理论预测值一致。Northern杂交及PCR检测表明该基因主要表达在成人在及胚胎胪组织,在K562和MO7e两株人髓性白血病细胞系中也有较高丰度表达。氯高铁血红素及红细胞生成素EPO（erythropoietin）诱导K562细胞向红系分化过程中,EDAG－1的表达随细胞的分化迅速下调;这些结果提示EDAG－1可能是一种与造血细胞分化调控密切相关的新基因。     

Regulation of phospholamban and troponin-I phosphorylation in the intact rat cardiomyocytes by adrenergic and cholinergic stimuli: roles of cyclic nucleotides,calcium, protein kinases and phosphatases and depolarization

Protein phosphorylation was investigated in [³²P]-labeled cardiomyocytes isolated from adult rat heart ventricles. The -adrenergic stimulation (by isoproterenol, ISO) increased the phosphorylation of inhibitory subunit of troponin (TN-I), C-protein and phospholamban (PLN). Such stimulation was largely mediated by increased adenylyl cyclase (AC) activity, increased myoplasmic cyclic AMP and increased cyclic AMP dependent protein kinase (A-kinase)-catalyzed phosphorylation of these proteins in view of the following observations: (a) dibutyryl-and bromo-derivatives of cyclic AMP mimicked the stimulatory effect of ISO on protein phosphorylation while (b) Rp-cyclic AMP was found to attenuate ISO-dependent stimulation. Unexpectedly, 8-bromo cyclic GMP was found to markedly increase TN-I and PLN phosphorylation. Both ₁- and ₂-adrenoceptors were present and ISO binding to either receptor was found to stimulate myocyte AC. However, the stimulation of the ₂-AR only marginally increased while the stimulation of ₁-AR markedly increased PLN phosphorylation. Other stimuli that increase tissue cyclic AMP levels also increased PLN and TN-I phosphorylation and these included isobutylmethylxanthine (non-specific phosphodiesterase inhibitor), milrinone (inhibits cardiotonic inhibitable phosphodiesterase, sometimes called type III or IV) and forskolin (which directly stimulates adenylyl cyclase). Cholinergic agonists acting on cardiomyocyte M₂-muscarinic receptors that are coupled to AC via pertussis toxin(PT)-sensitive G proteins inhibited AC and attenuated ISO-dependent increases in PLN and TN-I phosphorylation. Thein vivo PT treatment, which ADP-ribosylated G_i-like protein(s) in the myocytes, markedly attenuated muscarinic inhibitory effect on PLN and TN-I phosphorylation on one hand and, increased the -adrenergic stimulation, on the other. Controlled exposure of isolated myocytes to N-ethyl maleimide, also led to the findings similar to those seen following the PT treatment. Exposure of myocytes to phorbol, 12-myristate, 13-acetate (PMA) increased the protein phosphorylation, augmenting the stimulation by ISO, and such augmentation was antagonized by propranolol suggesting modulation of the -adrenoceptor coupled AC pathway by PMA. Okadaic acid (OA) exposure of myocytes also increased protein phosphorylation with the results supporting the roles for type 1 and 2A protein phosphatases in the dephosphorylation of PLN and TN-I. Interestingly OA treatment attenuated the muscarinic inhibitory effect which was restored by subsequent brief exposure of myocytes to PMA. While the stimulation of alpha adrenoceptors exerted little effect on the phosphorylation of PLN and TN-I, inactivation of alpha adrenoceptors by chloroethylclonidine (CEC), augmented -adrenergically stimulated phosphorylation. KCl-dependent depolarization of myocytes was observed to potentiate ISO-dependent increase in phosphorylation (incubation period 15 sec to 1 min) as well as to accelerate the time-dependent decline in this phosphorylation seen upon longer incubation. Verapamil decreased ISO-stimulated protein phosphorylation in the depolarized myocytes. Depolarization was found to have little effect on the muscarinic inhibitory action on phosphorylation. Prior treatment of myocytes with PMA, was found to augment ISO-stimulated protein phosphorylation in the depolarized myocytes. Such augmented increases were completely blocked by propranolol. Forskolin also stimulated PLN and TN-I phosphorylation. Prior exposure of myocytes to forskolin followed by incubation in the depolarized and polarized media showed that PLN was dephosphorylated more rapidly in the depolarized myocytes. The results support the view that both cyclic AMP and calcium signals cooperatively increase the rates of phosphorylation of TN-I and PLN in the depolarized cardiomyocytes during -adrenergic stimulation. The results raise the additional possibility that the calcium signal may regulate the dephosphorylation of PLN in the depolarized cell. While muscarinic attenuation of -adrenergic action on protein phosphorylation was mediated, in part, by decreased AC activity, and muscarinic inhibition of AC and protein phosphorylation was not detectably influenced by the depolarization, the evidence was seen that muscarinic stimulation of dephosphorylation mechanisms are intimately involved. The postulate that the simultaneous stimulation of ₁-adrenoceptors inhibits -adrenergic stimulation of PLN and TN-I phosphorylation is supported.     

Influence of training in the dark or light phase on physiologic and metabolic parameters of Wistar rats submitted to aerobic exercise

Light and dark phase training may influences rodents’ physiologic parameters because these animals have nocturnal habits. Thus, we verify the effects of the training in different photoperiods on metabolism and corporal composition of rats. Eighteen rats were divided into three groups – G1: non-trained; G2: trained in the light phase; G3: trained in the dark phase. Rats were allowed to swim for 60 min, five times per week during six weeks. Trained animals presented a smaller weight gain and fat percentage in carcass. Rats of G3 increased gastrocnemius relative weight. The adipocyte diameter of G3 rats was smaller than the other groups. The levels of the total cholesterol, low-density proteins, and triacylglycerols were decreased in animals of G2 while the glycemia was increased. Training in light phase provided more alterations in the blood biochemical profile while the training in the dark increased the gastrocnemius weight and decreased the diameter of the adipocyte.     

Physical activity levels of normal-weight and overweight girls and boys during primary school recess

Objective: This study aimed to compare moderate‐to‐vigorous physical activity (MVPA) and vigorous physical activity (VPA) in normal‐weight and overweight boys and girls during school recess. Research Methods and Procedures: Four hundred twenty children, age 6 to 10 years, were randomly selected from 25 schools in England. Three hundred seventy‐seven children completed the study. BMI was calculated from height and weight measurements, and heart rate reserve thresholds of 50% and 75% reflected children's engagement in MVPA and VPA, respectively. Results: There was a significant main effect for sex and a significant interaction between BMI category and sex for the percent of recess time spent in MVPA and VPA. Normal‐weight girls were the least active group, compared with overweight boys and girls who were equally active. Fifty‐one boys and 24 girls of normal weight achieved the 40% threshold; of these, 30 boys and 10 girls exceeded 50% of recess time in MVPA. Eighteen overweight boys and 22 overweight girls exceeded the 40% threshold, whereas 8 boys and 8 girls exceeded the 50% threshold. Discussion: Overweight boys were significantly less active than their normal‐weight male counterparts; this difference did not hold true for girls. Even though nearly double the number of normal‐weight children achieved the 40% of MVPA during recess compared with overweight children, physical activity promotion in school playgrounds needs to be targeted not only at overweight but at other health parameters, as 40 overweight children met the 40% MVPA target proposed for recess.     

An Examination of the Relationship Between Resting Heart Rate Variability and Heart Rate Reactivity to a Mental Arithmetic Stressor

Resting heart rate variability can be an index of sympathetic or parasympathetic dominance, according to the frequency of the variability studied. Sympathetic dominance of this system has been linked to increased risk of cardiovascular disease (CVD). Similarly, rapid and dramatic increases in heart rate reactivity to a stressor task have also been suggested as indicating increased risk of CVD via atherogenesis. Although both of these variables have been related to the development of cardiovascular disease, and both may be related to increased sympathetic activity or parasympathetic withdrawal, most research studies have tended to focus on either variable independently of the other. In order to investigate whether these two indices of stressor reactivity were related in relatively young and healthy subjects, resting heart rate variability data were collected from 80 volunteers for 20 minutes. In addition, heart rate reactivity data were collected during a 2-minute mental arithmetic stressor, which has been previously shown to induce significant increases in heart rate. After classifying subjects according to whether their heart rate variability data were above or below the mean for their gender, heart rate reactivity data were examined via MANOVA to detect significant differences between subject groups. Females showed significant effects, and males showed nonsignificant trends, but these two sets of data were in different directions, suggesting that gender may be a confounding factor in the relationship between heart rate reactivity and heart rate variability.     

microRNAs参与韧带成纤维细胞成骨分化相关分子表达的调节

韧带成纤维细胞成骨分化与强直性脊柱炎等多种异位骨化相关性疾病有关,但其机制尚不清楚.本研究目的在于观察韧带成纤维细胞在成骨分化过程中microRNA和mRNA的表达谱变化,以期为揭示成纤维细胞成骨分化机制提供研究基础.原代培养韧带成纤维细胞、地塞米松、抗坏血酸和β 磷酸甘油体外诱导其成骨分化, RT-PCR检测成骨标志物骨钙素和Runx2的表达.采用表达谱基因芯片分析诱导0、7、14 d后韧带成纤维细胞的microRNAs和mRNAs表达,并用实时定量PCR（RT-qPCR）和Western印迹方法验证生物信息学分析结果.结果显示,与未诱导前相比,成骨分化第7 d有66个microRNAs和640个mRNA表达上调,94个microRNAs和744个mRNA表达下调;成骨分化第14 d有58个microRNAs和781个mRNA表达上调,96个microRNAs和603个mRNA表达下调.实时定量PCR和Western印迹验证结果显示,miR-29b在成骨分化过程中表达上调,TGFβ3表达水平降低,与芯片结果一致,miR-29b通过抑制TGFβ3蛋白的翻译来促进Runx2的表达,从而促进韧带成纤维细胞向成骨细胞分化.韧带成纤维细胞成骨分化过程中,microRNA调控基因及mRNA差异表达基因除涉及BMPs、Wnt和Ihh等信号通路外,在成纤维细胞成骨分化过程中可能还存在其它的新机制.     

Applications of the Poly-K Statistical Test to Life-Time Cancer Bioassay Studies

The statistical analysis of cancer bioassay data has historically depended on the pathological determination of the experimental animal's cause of death. The poly-k statistical test has provided a method of statistical analysis of animal bioassay data without the need for cause of death information. The test has been shown to have good statistical properties in the typical 2-year cancer bioassay. However, while the poly-k test has been applied to chronic lifetime animal studies, it has not been formally evaluated with respect to the operating characteristics of this statistical test when applied to such studies. Thus, our objective is to assess the performance of the poly-k test for lifetime studies and to make comparisons with other tests. We observed in one recent lifetime study of the gasoline additive methyl tertiary butyl ether (MTBE) that the application of the poly-k test was not statistically robust. Simulation studies were subsequently conducted for a limited number of scenarios of lifetime cancer bioassays. These simulations showed that the poly-k test is not statistically robust for testing effect of increasing dose in some lifetime cancer studies.     

采用关键点控制和反馈调节,提高微生物学实验课质量

将全面质量管理理论引入微生物学实验课教学,形成以关键点控制和反馈调节为核心的教学质量保障系统,实践证明,可有效地促进学生积极思考,提高实验技能。对教学过程中“关键点”．“关键点控制”的含义和特性以及“反馈信号”、“反馈调节”的含义和类型做了系统的阐述。以具体实验为例,详细说明了实验课教学中关键点控制和反馈调节的实施过程,对于保证教学质量和客观、公正地分析评价教学效果具有重要意义。     

鸡的DNA指纹与屠宰性能的相关性研究

利用SR92A系鸡与萧山♀鸡的杂交一代群体,以EA（禽内源性反转录病毒片段）为探针,限制性内切酶为EcORI,探讨DNA指纹与若干屠宰性能之间的相关性。结果表明EAV指纹图谱中,长度约为4kb的条带J与SR92A系×萧山鸡杂交后代75日龄的活重、屠宰重、半净膛重、爪重、胸肌重、头重、大腿重有显著负相关,无J带的个体与有J带的相比,75日龄活重平均高出280克,屠宰重高出257克,半净膛重高出216克,胸肌重高出16．71克,分别高达28．57％、28．87％、28．76％和54．00％。若在亲本中选择无条带J的个体建立无J带的后代群体,根据算式：△W＝（XJ-－XJ ）×N×FJ 预测,选择效果和经济效益显著。     

24-Hour Variation in the Reactivity of Rate-Pressure-Product to Everyday Physical Activity in Patients Attending a Hypertension Clinic

The exercise-related response of the rate-pressure-product (RPP) is a prognostic marker of autonomic imbalance, cardiovascular mortality, and silent myocardial ischemia in hypertension. In view of the well-known 24 h variation in out-of-hospital sudden cardiac events, our aim was to investigate whether the reactivity of RPP to everyday physical activities varies over the 24 h. Ambulatory measurements of systolic blood pressure (BP) and heart rate were recorded every 20 min for 24 h in 440 diurnally active patients attending a hypertension clinic. Wrist activity counts were summed over the 15 min that preceded a BP measurement. An RPP reactivity index was derived for each of twelve 2 h data bins by regressing the change in RPP against the change in logged activity counts. The RPP showed 24 h variation (p?<?0.0005), with a peak of 11,004 (95% CI?=?10,757 to 11,250) beat?·?min^?1?·?mmHg occurring at 10:00 h (2 h after mean wake-time). The overall 24 h mean of RPP reactivity was 477 beat?·?min^?1?·?mmHg?·?logged activity counts^?1 (95% CI?=?426 to 529). The largest increase in RPP reactivity occurred within the first 2 h after waking (p?<?0.0005). There were no subsequent significant differences in RPP reactivity up to 14 h after waking. The lowest RPP reactivity was found 18–20 h after waking, with a peak-to-trough variation of 593 beat?·?min^?1?·?mmHg?·?logged activity counts^?1 (95% CI?=?394 to 791, p?<?0.0005). Although this variation was not moderated by BP status, age, or sex, less variability in RPP reactivity was found for the medicated individuals during the waking hours. These data suggest that under conditions of normal living, the reactivity of RPP to a given change in physical activity increases markedly during the first 2 h after waking from nocturnal sleep, the time when out-of-hospital sudden cardiac events are also most common. Therefore, these data add weight to the notion that reactivity of RPP to physical activity could be a prognostic marker of autonomic imbalance and cardiovascular mortality, although more research is needed to assess the specific prognostic value of 24 h ambulatory measurements of RPP and physical activity.     

单胺氧化酶B单核苷酸基因多态性与犬旷场行为关联分析

采用旷场行为测试方法, 测定204条德国牧羊犬、拉布拉多犬、史宾格犬二月龄幼犬在新异环境下的兴奋性和探索活动, 同时应用RFLP-PCR方法检测单胺氧化酶B(Monoamine Oxidase B, MAOB)基因的多态性, 分析MAOB基因的基因型和基因频率在品种间的分布差异以及基因多态性与旷场测验中行为参数的相互关系, 发现MAOB基因型频率与基因频率在犬品种之间差异极显著(P<0.01), MAOB基因型与幼犬在旷场中的走动时间、趴卧时间、跨格次数、站立扒墙次数有关(P<0.01或P<0.05), 对运动姿势改变次数也有一定影响(P=0.064)。其中, TT基因型犬的走动时间和跨格次数均高于TC型和CC型犬(P<0.05), 运动姿势改变次数和站立扒墙次数高于CC型犬(P<0.05); 而CC型个体的趴卧时间高于TT型个体(P<0.05)。MAOB基因对走动时间和跨格次数的加性遗传效应达极显著(P<0.01), 对运动姿势改变次数、站立扒墙次数和趴卧时间有显著的加性效应(P<0.05)。实验结果表明, MAOB基因与幼犬在旷场测验中的运动、兴奋性和探索活动有关, TT基因型对运动、兴奋性和探索活动具有正遗传效应。     

Autonomic Nervous System Activity and the State and Development of Obesity in Japanese School Children

Objective: The autonomic nervous system (ANS) plays an important role in regulating energy expenditure and body fat content; however, the extent to which the ANS contributes to pediatric obesity remains inconclusive. The aim of this study was to evaluate whether sympathetic and/or the parasympathetic nerve activities were altered in an obese pediatric population. We further examined a physiological association between the duration of obesity and the sympatho‐vagal activities to scrutinize the nature of ANS alteration as a possible etiologic factor of childhood obesity. Research Methods and Procedures: Forty‐two obese and 42 non‐obese healthy sedentary school children were carefully selected from 1080 participants initially recruited to this study. The two groups were matched in age, gender, and height. The clinical records of physical characteristics and development of the obese children were retrospectively reviewed to investigate the onset and progression of obesity. The ANS activities were assessed during a resting condition by means of heart rate variability power spectral analysis, which enables us to identify separate frequency components, i.e., total power (TP), low‐frequency (LF) power, and high‐frequency (HF) power. The spectral powers were then logarithmically transformed for statistical testing. Results: The obese children demonstrated a significantly lower TP (6.77 ± 0.12 vs. 7.11 ± 0.04 ln ms², p < 0.05), LF power (6.16 ± 0.12 vs. 6.42 ± 0.05 ln ms², p < 0.05), and HF power (5.84 ± 0.15 vs. 6.34 ± 0.07 ln ms², p < 0.01) compared with the non‐obese children. A partial correlation analysis revealed that the LF and HF powers among 42 obese children were negatively associated with the duration of obesity independent of age (LF: partial r = ?0.55, p < 0.001; HF: partial r = ?0.40, p < 0.01). The obese children were further subdivided into two groups based on the length of their obesity. All three spectral powers were significantly reduced in the obese group with obesity of >3 years (n = 18) compared to the group with obesity of <3 years. Discussion: Our data indicate that obese children possess reduced sympathetic as well as parasympathetic nerve activities. Such autonomic depression, which is associated with the duration of obesity, could be a physiological factor promoting the state and development of obesity. These findings further imply that preventing and treating obesity beginning in the childhood years could be an urgent and crucial pediatric public health issue.     

植物与病原真菌互作的形态变化及其生理、生化机制和基因调控

本文从生理、生化、酶学及基因调控等方面对植物与病原真菌互作过程中的形态变化进行了综述,以期为植物抗病方面的研究提供参考